Microtubule-associated protein tau (MAPT) pre-mRNA and mRNA (MAPT pre-mRNA/mRNA)

Microtubule-associated protein tau (MAPT) pre-mRNA and mRNA are the primary transcripts derived from the MAPT gene, which encodes the tau protein essential for microtubule assembly and stability in the central nervous system (NCBI Gene ID: 4137). In various neurodegenerative disorders known as tauopathies, including Alzheimer's disease and frontotemporal dementia, tau protein undergoes pathological changes such as hyperphosphorylation and aggregation into neurofibrillary tangles (Gao et al., 2018, Neuron). Therapeutic targeting of MAPT mRNA and pre-mRNA aims to reduce the overall expression of tau or modulate the alternative splicing of exon 10, which determines the ratio of 3-repeat (3R) to 4-repeat (4R) tau isoforms (Mummery et al., 2023, Nature Medicine). Antisense oligonucleotides (ASOs), such as BIIB080, are designed to bind these transcripts and induce RNase H-mediated degradation or steric hindrance of splicing factors (De Vos et al., 2017, Science Translational Medicine). By decreasing the pool of available tau protein, these interventions seek to prevent the formation of toxic aggregates and preserve neuronal integrity.

Other names

Tau mRNAMAPT transcriptTau pre-messenger RNAMicrotubule-associated protein tau RNA

Antisense oligonucleotides (ASOs) bind to the MAPT mRNA or pre-mRNA to induce RNase H-mediated degradation, thereby reducing tau protein expression, or to modulate alternative splicing of exon 10 to balance tau isoforms.